1. Field of the Invention
The present invention relates to a novel cytocidal modified immunoglobulin and a process for the preparation thereof, and more particularly relates to a novel cytocidal modified immunoglobulin comprising an immunoglobulin, which is capable of selectively binding to a particular antigen possessed by a cell to be killed (hereinafter referred to as a target cell), or its fragment having an antigen-binding moiety, whose amino group is linked with a mitomycin C derivative and a process for the preparation thereof.
2. Description of the Prior Art
It is a publicly known art to have the carboxyl group of an antibody linked with mitomycin C by allowing a large quantity of mitomycin C to contact with an antibody protein in the presence of water-soluble carbodiimide (Japanese Patent Application Laid-open No. 92325/80).
In this publicly known method in which a condensing agent of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide is used as a means for forming the amide linkage between the amino group and the carboxyl group, undesirable phenomena such as an intramolecular reaction between the amino group and carboxyl group in the molecule of an antibody protein and an intermolecular reaction between such groups of the antibody molecules take place, thus causing a considerable loss of the antigen-recognizing activity of the antibody or the formation of macromolecular aggregates whose presence in the drugs is undesirable.
To minimize such undesirable phenomena, mitomycin C which constitutes the amino component to be used in the abovementioned method must necessarily be used in a large excess in the reaction. This is not an advantageous mode of production from the industrial viewpoint.
There is another publicly known method of obtaining a conjugate of an antibody and mitomycin C by treating the antibody protein with cyanogen bromide, followed by the treatment with a large quantity of mitomycin C (Japanese Patent Application Laid-open No. 135421/51). However, this procress can hardly be said to be useful from the industrial viewpoint because in the conjugate obtained according to this method, only one molecule of mitomycin C is linked with the antibody protein molecule.